Lindsey Farmer

 Introduction Autism Spectrum Disorder (ASD) includes a range of developmental neuro-behavioral disorders characterized by restricted and repetitive behavior, abnormal social interaction and impaired communication^1,2,7. 1 in 68 people in the US have ASD, and the prevalence has increased over 10 fold in the last 40 years, representing some of the greatest burden of childhood disease¹¹. Up to 83% of ASD patients experience co-morbidities, including GI disturbances and particular eating habits⁵. Research suggests that ASD children have an overgrowth of Clostridium in their microbial flora, leading to an overproduction of bacterial metabolites such as HPHPA, propionic acid (PPA), and butyrate (BA)^1,2,6,7,9,10. These metabolites could be neurotoxic and induce autistic behaviors^1,2,4,6. How these kids acquire dysbiosis is yet to be elucidated, but the data suggest a potential antibiotic/probiotic or fecal transplant therapy for ASD. Methods A murine model of ASD (mice exposed to valproic acid in utero) was used to determine the relationship between gut microbiota and autism-like behavior. Sequencing technology was used to determine microbiota composition and levels of short chain fatty acids (SCFA) and lactic acid in caecal content¹. 8 different rats were administered 250 mg/kg oral PPA and 8 controls were given saline. Markers for oxidative stress, neurotransmission, energy metabolism, apoptosis, and neuroinflammation were measured in brain tissue homogenates⁴. Results The valproic acid exposed mice had affected levels of Bacteroidetes and Firmicutes, supporting the data from human studies of ASD. The microbial differences were seen more drastically in the male mice, mirroring the human disease’s preponderance for males. Increased levels of butyrate and decreased social behavior scores were denoted². Similar behavioral abnormalities reflecting ASD characteristics were observed in the PPA exposed rats, along with an increase in oxidative stress markers, decrease in glutathione, impaired energy metabolism, and elevated inflammation/pro-apoptotic markers⁴.  Conclusion The data support that autistic behavior can be linked to the gut microbiome and are related to altered microbial colonization and activity in mice models. The effects of overgrowth of bacteria, such as Clostridia, lead to increased levels of short chain fatty acids such as PPA which proved to be neurotoxic and induce autistic behavior. The study points to the microbiome as a main etiological agent in the biochemical features of autistic patients and suggest microbiome manipulation as a future treatment option.

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